title: Protein wrapping: a molecular marker for association, aggregation and drug design.
abstract: In this tutorial review we survey the concept of protein wrapping from a physico-chemical perspective. Wrapping is introduced as an indicator of the packing quality of protein structure. Thus, while a well-wrapped protein is sustainable in isolation, a poorly wrapped protein is reliant on binding partnerships to maintain its structural integrity. At a local level, wrapping is indicative of the extent of solvent exposure of the amide-carbonyl hydrogen bonds of the protein backbone. Poorly wrapped hydrogen bonds, the so-called dehydrons, are shown to represent structural vulnerabilities. These singularities are sticky, hence promoters of protein associations. We also focus on severely under-wrapped protein structures that belong to an order/disorder twilight. Such proteins are shown to be prone to aggregate. Finally, we survey the recent exploitation of dehydrons as targetable features to promote specificity in drug-based cancer therapy. Dehydrons prove to be valuable targets to reduce side effects and enhance drug safety.
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX 77005, USA. arifer@rice.edu
authors.forename: Ariel
authors.initials: A
authors.lastname: Fernández
authors.forename: Alejandro
authors.initials: A
authors.lastname: Crespo
mesh_terms: D015195:Drug Design; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
chemical_list: D011506:Proteins; D014867:Water